A role for p75 neurotrophin receptor in the control of hair follicle morphogenesis
A role for p75 neurotrophin receptor in the control of hair follicle morphogenesis
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DOI：
10.1006/dbio.1999.9464
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发表时间：
1999-12-01
影响因子：
2.7
通讯作者：
Paus, R
中科院分区：
文献类型：
--
作者：
Botchkareva, NV;Botchkarev, VA;Paus, R
据报道，在毛囊 (HF) 形态发生过程中，p75 神经营养蛋白受体 (p75NTR) 是第一个被发现由后来发育成 HF 真皮乳头 (DP) 的成纤维细胞表达的生长因子受体。然而，p75NTR 在 HE 形态发生中的功能作用仍不清楚。研究胎儿和新生儿 C57BL/6 小鼠背部皮肤的 HE 发育，我们发现在 HF 发育的早期阶段，p75NTR 免疫反应性 (IR) 在 DP 成纤维细胞以及皮肤神经中显着表达。相反，p75NTR-IR在完全发育的HP中从DP中消失，并且仅在HF的上皮外根鞘中表达。与年龄匹配的野生型动物相比，p75NTR 敲除（-/-）小鼠显示出 HF 形态发生显着加速，p75NTR 敲除小鼠的 DP 成纤维细胞显示原位增殖活性降低，表明其从增殖到分化的转变发生了变化。尽管p75NTR敲除小鼠和野生型小鼠的DP之间粘附分子（NCAM）、选定的形态发生素（TGF beta-2、HGF/SE、FGF-2、KGF）或其受体（TGF beta R-II、m-met、FGFR-1）的表达没有显着差异，但p75NTR突变体显示FGFR-2的显着上调， 滤泡 DP 和上皮细胞中 KGF 的高亲和力受体。此外，给予抗KGF中和抗体可显着抑制体内p75NTR敲除小鼠的HF形态发生的加速。这些观察结果表明，p75NTR 在 HE 形态发生过程中发挥着重要作用，作为负向控制 HF 发展的受体，最有可能通过 DP 成纤维细胞增殖/分化的改变以及通过 HF 中 KGF/FGFR-2 信号传导的下调。 (C) 1999 年学术出版社。
During hair follicle (HF) morphogenesis, p75 neurotrophin receptor (p75NTR) reportedly is the first growth factor receptor found to be expressed by those fibroblasts that later develop into the dermal papilla (DP) of the HF. However, the functional role of p75NTR in HE morphogenesis is still unknown. Studying HE development in fetal and neonatal C57BL/6 murine back skin, we show that p75NTR-immunoreactivity (IR) is prominently expressed by DP fibroblasts as well as by skin nerves during the early steps of HF development. In contrast, p75NTR-IR disappears from the DP in the fully developed HP and it is expressed only in the epithelial outer root sheath of the HF. Compared to age-matched wild-type animals, p75NTR knockout (-/-) mice show significant acceleration of HF morphogenesis, and DP fibroblasts of p75NTR knockout mice show reduced proliferative activity in situ, indicating alterations in their transition from proliferation to differentiation. Although no significant differences in the expression of adhesion molecules (NCAM), selected morphogens (TGF beta-2, HGF/SE, FGF-2, KGF), or their receptors (TGF beta R-II, m-met, FGFR-1) were seen between DP of p75NTR knockout and wild-type mice, p75NTR mutants showed a prominent upregulation of FGFR-2, a high-affinity receptor for KGF, in both follicular DP and epithelium. furthermore, the administration of anti-KGF neutralizing antibody significantly inhibited acceleration of HF morphogenesis in p75NTR knockout mice in vivo. These observations suggest that p75NTR plays an important role during HE morphogenesis, functioning as a receptor that negatively controls HF development, most likely via alterations in DP fibroblast proliferation/differentiation and via downregulation of KGF/FGFR-2 signaling in the HF. (C) 1999 Academic Press.